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Digestive Diseases and Sciences
Published in: Digestive Diseases and Sciences 4/2016

01-04-2016 | Original Article

Developmental Stage-Specific Embryonic Induction of HepG2 Cell Differentiation

Authors: Yanning Li, Yanhong Zong, Zhigang Xiao, Mengxuan Zhu, Hui Xiao, Jinsheng Qi, Kun Liu, Hui Wang

Published in: Digestive Diseases and Sciences | Issue 4/2016

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Abstract

Background

Although hepatocellular carcinoma cells can sometimes undergo differentiation in an embryonic microenvironment, the mechanism is poorly understood.

Aim

The developmental stage-specific embryonic induction of tumor cell differentiation was investigated.

Methods

Both chick and mouse liver extracts and hepatoblast-enriched cells at different developmental stages were used to treat human hepatoma HepG2 cells, and the effects on the induction of differentiation were evaluated. The nuclear factors controlling differentiation, hepatocyte nuclear factor (HNF)-4α, HNF-1α, HNF-6 and upstream stimulatory factor-1 (USF-1), and the oncogene Myc and alpha-fetoprotein (AFP) were measured. HNF-4α RNA interference was used to verify the role of HNF-4α. Embryonic induction effects were further tested in vivo by injecting HepG2 tumor cells into immunodeficient nude mice.

Results

The 9–11-days chick liver extracts and 13.5–14.5-days mouse hepatoblast-enriched cells could inhibit proliferation and induce differentiation of HepG2 cells, leading to either death or maturation to hepatocytes. The maturation of surviving HepG2 cells was confirmed by increases in the expressions of HNF-4α, HNF-1α, HNF-6, and USF-1, and decreases in Myc and AFP. The embryonic induction of HepG2 cell maturation could be attenuated by HNF-4α RNA interference. Furthermore, the 13.5-days mouse hepatoblast culture completely eliminated HepG2 tumors with inhibited Myc and induced HNF-4α, confirming this embryonic induction effect in vivo.

Conclusions

This study demonstrated that developmental stage-specific embryonic induction of HepG2 cell differentiation might help in understanding embryonic differentiation and oncogenesis.
Appendix
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Metadata
Title
Developmental Stage-Specific Embryonic Induction of HepG2 Cell Differentiation
Authors
Yanning Li
Yanhong Zong
Zhigang Xiao
Mengxuan Zhu
Hui Xiao
Jinsheng Qi
Kun Liu
Hui Wang
Publication date
01-04-2016
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 4/2016
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-015-3966-4

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